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Viktor Hegedus - One of the best experts on this subject based on the ideXlab platform.

  • structural evidence for counter current flow in proximal tubules versus pertitubular Capillaries in the rat kidney evaluation of the counter current mechanism between the proximal convoluted tubules and the Peritubular Capillaries in the rat nephron
    Apmis, 2000
    Co-Authors: Poul Faarup, Nielshenrik Holsteinrathlou, Viktor Hegedus
    Abstract:

    BACKGROUND: In spite of the very high exchange of water and solutes between the proximal tubules and the Peritubular Capillaries, very little is known about flow directions in these two interrelated structures. We therefore developed a morphological technique suitable for the quantitative evaluation of a counter-current system between the proximal convoluted tubules and the Peritubular Capillaries in rat renal cortex. METHODS: In male pentothal-anesthetized Wistar rats (body weight 200-250 g), India ink was injected into the aorta above the renal arteries, followed by instant freezing of the right kidney in isopentane at -165 degrees C, and subsequent freeze-substitution in alcohol. In microscopic slides from kidneys in which only 20-55% of the cortical Peritubular capillary loops was filled with ink--representing the arterial end of the Capillaries--and in which the proximal tubular segmentation could be identified in PAS-stained sections, the segments of the convoluted proximal tubules were quantitatively compared with regard to the presence of ink-stained and unstained Peritubular Capillaries in nephrons from the whole renal cortex. RESULTS: In the microscopic specimens of the five animals used both the loops from the first segment (P1) of the proximal convoluted tubule and those of the second segment (P2) were systematically packed closely together, the transitional segment (P1-2) being interposed between the groups. Around the loops of P1, 8%+/-2% of the Capillaries was stained with India ink. In contrast, surrounding the P2 loops 67%+/-5% of the Capillaries contained ink, significantly exceeding that for P1 (p<0.01). CONCLUSION: Throughout the rat renal cortex, the most proximal fraction of the Peritubular Capillaries surrounds the second segments of the proximal convoluted tubules, while the first tubular segments are surrounded by the more distal fraction of the Peritubular Capillaries. Consequently, the flows in the Peritubular Capillaries and in the proximal convoluted tubules in the rat renal cortex are systematically arranged as a counter-current system. This feature was previously identified only in superficial nephrons.

  • Structural evidence for counter-current flow in proximal tubules versus pertitubular Capillaries in the rat kidney. Evaluation of the counter-current mechanism between the proximal convoluted tubules and the Peritubular Capillaries in the rat nephron
    Apmis, 2000
    Co-Authors: Poul Faarup, Niels-henrik Holstein-rathlou, Viktor Hegedus
    Abstract:

    BACKGROUND: In spite of the very high exchange of water and solutes between the proximal tubules and the Peritubular Capillaries, very little is known about flow directions in these two interrelated structures. We therefore developed a morphological technique suitable for the quantitative evaluation of a counter-current system between the proximal convoluted tubules and the Peritubular Capillaries in rat renal cortex. METHODS: In male pentothal-anesthetized Wistar rats (body weight 200-250 g), India ink was injected into the aorta above the renal arteries, followed by instant freezing of the right kidney in isopentane at -165 degrees C, and subsequent freeze-substitution in alcohol. In microscopic slides from kidneys in which only 20-55% of the cortical Peritubular capillary loops was filled with ink--representing the arterial end of the Capillaries--and in which the proximal tubular segmentation could be identified in PAS-stained sections, the segments of the convoluted proximal tubules were quantitatively compared with regard to the presence of ink-stained and unstained Peritubular Capillaries in nephrons from the whole renal cortex. RESULTS: In the microscopic specimens of the five animals used both the loops from the first segment (P1) of the proximal convoluted tubule and those of the second segment (P2) were systematically packed closely together, the transitional segment (P1-2) being interposed between the groups. Around the loops of P1, 8%+/-2% of the Capillaries was stained with India ink. In contrast, surrounding the P2 loops 67%+/-5% of the Capillaries contained ink, significantly exceeding that for P1 (p

Robert B. Colvin - One of the best experts on this subject based on the ideXlab platform.

  • Novel Quantitative Method to Evaluate Globotriaosylceramide Inclusions in Renal Peritubular Capillaries by Virtual Microscopy in Patients With Fabry Disease
    Archives of Pathology & Laboratory Medicine, 2012
    Co-Authors: Laura Barisoni, Robert B. Colvin, J. Charles Jennette, Sheela Sitaraman, Alexander Bragat, Jeff Castelli, Dan Walker, Pol Boudes
    Abstract:

    Context.—Assessing the amount of globotriaosylceramide inclusions in renal Peritubular Capillaries by a semiquantitative approach is a standard and useful measure of therapeutic efficacy in Fabry d...

  • Persistent rejection of Peritubular Capillaries and tubules is associated with progressive interstitial fibrosis
    Kidney International, 2002
    Co-Authors: Akira Shimizu, Kazuhiko Yamada, David H. Sachs, Robert B. Colvin
    Abstract:

    Persistent rejection of Peritubular Capillaries and tubules is associated with progressive interstitial fibrosis Background We have reported that a 12-day course of high dose cyclosporine A treatment in thymectomized miniature swine with major histocompatibility complex (MHC) class I-mismatched renal allografts results in transient acute rejection followed by either in chronic rejection (progression group) or graft acceptance (recovery group). Here, we examined the differential features between both groups in the Peritubular Capillaries (PTCs) and tubules to clarify the pathogenesis of the progressive interstitial fibrosis in chronic rejection. Methods Morphometric and immunohistochemical studies were performed on serial renal biopsies (days 0 to 100) obtained from both groups, focusing on the cellular infiltrate, rejection of PTCs and tubules, myofibroblast accumulation, and progressive interstitial fibrosis. Results In the progression group, acute rejection occurred by day 8 and progressed to chronic rejection by day 100, with the development of interstitial fibrosis. PTC endothelial cell and tubular epithelial cell death associated with CD3+ cell infiltration was evident, confirmed by nick end-labeling (TUNEL), commencing by day 8 and continuing thereafter. In acute rejection, destruction of PTCs and tubules accompanied by disruption of basement membrane (BM) occurred with capillaritis or tubulitis in areas with a severe cellular infiltrate. During the development of chronic rejection, capillaritis of PTCs and tubulitis continued by day 100, accompanied by persistent T cell infiltration, and the remaining PTCs and tubules exhibited progressive atrophy with thickening and/or lamination of BM. On day 100, identifiable PTCs and tubules were lost in areas of interstitial fibrosis. Proliferating (PCNA+) α-actin+ myofibroblasts accumulated around PTCs, tubules and in interstitium, and widespread interstitial fibrosis developed by day 100. In contrast, in the recovery group, injured PTCs and tubules recovered by day 100 based on the resolution of acute rejection, and minimal loss of PTCs and tubules was evident by day 100 with minimal interstitial fibrosis. Conclusions Persistent rejection directed at PTCs and tubules, and proliferation of myofibroblasts are prominent features in the progressive interstitial fibrosis in chronic rejection, and are probably key events in its pathogenesis.

  • chronic humoral rejection identification of antibody mediated chronic renal allograft rejection by c4d deposits in Peritubular Capillaries
    Journal of The American Society of Nephrology, 2001
    Co-Authors: Shamila Mauiyyedi, Eveline E. Schneeberger, Manuel Pascual, Susan L. Saidman, Winfred W. Williams, Patricia Della Pelle, Bernard A Collins, Nina Tolkoffrubin, Benedict A Cosimi, Robert B. Colvin
    Abstract:

    Abstract . The pathogenesis of chronic renal allograft rejection (CR) remains obscure. The hypothesis that a subset of CR is mediated by antidonor antibody was tested by determining whether C4d is deposited in Peritubular Capillaries (PTC) and whether it correlates with circulating antidonor antibodies. All cases (from January 1, 1990, to July 31, 1999) that met histologic criteria for CR and had frozen tissue (28 biopsies, 10 nephrectomies) were included. Controls were renal allograft biopsies with chronic cyclosporine toxicity ( n = 21) or nonspecific interstitial fibrosis ( n = 10), and native kidneys with end-stage renal disease ( n = 10) or chronic interstitial fibrosis ( n = 5). Frozen sections were stained by two-color immunofluorescence for C4d, type IV collagen and Ulex europaeus agglutinin I. Antidonor HLA antibody was sought by panel-reactive antibody analysis and/or donor cross matching in sera within 7 wk of biopsy. Overall, 23 of 38 CR cases (61%) had PTC staining for C4d, compared with 1 of 46 (2%) of controls ( P P P = 0.05). Since August 1998, five of six C4d-positive CR cases have been treated with mycophenolate mofetil ± tacrolimus with a 100% 1-yr graft survival, versus 40% before August 1998 ( P

  • Rejection of Peritubular Capillaries in renal allo‐ and xeno‐grafts
    Clinical Transplantation, 2000
    Co-Authors: Akira Shimizu, Robert B. Colvin, Nobuaki Yamanaka
    Abstract:

    The microvasculature plays an important role in the pathogenesis of humoral- and cell-mediated renal allo- and xeno-graft rejection. Peritubular capillary (PTC) endothelium expresses the major histocompatibility complex (MHC) class I and II antigens in the resting phase, as does the glomerular capillary endothelium, suggesting that these cells may be major immune targets. However, the role of PTCs in renal allo- and xeno-graft rejection is unclear. In this review, we discuss injury and subsequent remodeling of PTCs in both humoral- and cell-mediated rejection in allo- and xeno-grafts. Recent evidence suggests that PTC injury and endothelial cell death occur during both cell- and humoral-mediated rejection. Severe PTC rejection contributes to deterioration of graft function and acute graft loss. The mild but recurrent form of PTC rejection is associated with progressive interstitial fibrosis and chronic rejection. Following endothelial injury, the remaining PTC endothelium activates with up-regulation of allo-antigens and adhesion molecules, and down-regulation of anti-coagulant proteins. Subsequent to this, more severe rejection and graft dysfunction occur. Therefore, a careful analysis of cellular- and antibody-mediated rejection in PTCs is important in the diagnosis of rejection, prediction of graft prognosis, and in further development of new anti-rejection therapies.

  • Rejection of Peritubular Capillaries in renal allo- and xeno-graft.
    Clinical Transplantation, 2000
    Co-Authors: Akira Shimizu, Robert B. Colvin, Nobuaki Yamanaka
    Abstract:

    The microvasculature plays an important role in the pathogenesis of humoral- and cell-mediated renal allo- and xeno-graft rejection. Peritubular capillary (PTC) endothelium expresses the major histocompatibility complex (MHC) class I and II antigens in the resting phase, as does the glomerular capillary endothelium, suggesting that these cells may be major immune targets. However, the role of PTCs in renal allo- and xeno-graft rejection is unclear. In this review, we discuss injury and subsequent remodeling of PTCs in both humoral- and cell-mediated rejection in allo- and xeno-grafts. Recent evidence suggests that PTC injury and endothelial cell death occur during both cell- and humoral-mediated rejection. Severe PTC rejection contributes to deterioration of graft function and acute graft loss. The mild but recurrent form of PTC rejection is associated with progressive interstitial fibrosis and chronic rejection. Following endothelial injury, the remaining PTC endothelium activates with up-regulation of allo-antigens and adhesion molecules, and down-regulation of anti-coagulant proteins. Subsequent to this, more severe rejection and graft dysfunction occur. Therefore, a careful analysis of cellular- and antibody-mediated rejection in PTCs is important in the diagnosis of rejection, prediction of graft prognosis, and in further development of new anti-rejection therapies.

Adrian S. Woolf - One of the best experts on this subject based on the ideXlab platform.

  • Dysmorphogenesis of kidney cortical Peritubular Capillaries in angiopoietin-2-deficient mice.
    American Journal of Pathology, 2004
    Co-Authors: Jolanta E. Pitera, Adrian S. Woolf, Nicholas W. Gale, George D. Yancopoulos, Hai Tao Yuan
    Abstract:

    Angiopoietin-2 (Ang-2) modulates Tie-2 receptor activation. In mouse kidney maturation, Ang-2 is expressed in arteries, with lower levels in tubules, whereas Tie-2 is expressed by endothelia. We hypothesized that Ang-2 deficiency disrupts kidney vessel patterning. The normal renal cortical Peritubular space contains fenestrated Capillaries, which have few pericytes; they receive water and solutes which proximal tubules reclaim from the glomerular filtrate. In wild-type neonates, α smooth muscle actin (αSMA), platelet-derived growth factor receptor β (PDGFRβ), and desmin-expressing cells were not prominent in this compartment. In Ang-2 null mutants, αSMA, desmin, and PDGFRβ prominently immunolocalized in cortical Peritubular locations. Some αSMA-positive cells were closely associated with CD31- and Tie-2-positive Peritubular capillary endothelia, and some of the αSMA-positive cells expressed PDGFRβ, desmin, and neural/glial cell 2 (NG2), consistent with a pericyte-like identity. Immunoblotting suggested an increase of total and tyrosine-phosphorylated Tie-2 proteins in null mutant versus wild-type kidneys, and electron microscopy confirmed disorganized Capillaries and adjacent cells in cortical Peritubular spaces in mutant neonate kidneys. Hence, Ang-2 deficiency causes dysmorphogenesis of cortical Peritubular Capillaries, with adjacent cells expressing pericyte-like markers; we speculate the latter effect is caused by disturbed paracrine signaling between endothelial and surrounding mesenchymal precursor cells.

  • Peritubular capillary loss after mouse acute nephrotoxicity correlates with down regulation of vascular endothelial growth factor a and hypoxia inducible factor 1α
    American Journal of Pathology, 2003
    Co-Authors: Hai Tao Yuan, Jolanta E. Pitera, Xiaozhong Li, David A Long, Adrian S. Woolf
    Abstract:

    Although the response of kidneys acutely damaged by ischemia or toxins is dominated by epithelial destruction and regeneration, other studies have begun to define abnormalities in the cell biology of the renal microcirculation, especially with regard to Peritubular Capillaries. We explored the integrity of Peritubular Capillaries in relation to expression of vascular endothelial growth factor (VEGF)-A, hypoxia-inducible factor (HIF)-α proteins, and von Hippel-Lindau protein (pVHL) in mouse folic acid nephropathy, a model in which acute tubular damage is followed by partial regeneration and progression to patchy chronic histological damage. Throughout a period of 14 days, in areas of cortical tubular atrophy and interstitial fibrosis, loss of VEGFR-2 and platelet endothelial cell adhesion molecule-expressing Peritubular Capillaries was preceded by marked decreases in VEGF-A transcript and protein levels. Nephrotoxicity was associated with tissue hypoxia, especially in regenerating tubules, as assessed by an established in situ method. Despite the hypoxia, levels of HIF-1α, a protein known to up-regulate VEGF-A, were reduced. During the course of nephrotoxicity, levels of pVHL, a factor that destabilizes HIF-1α, increased significantly. We speculate that that down-regulation of VEGF-A may be functionally-implicated in the progressive attrition of Peritubular Capillaries in areas of tubular atrophy and interstitial fibrosis; VEGF-A down-regulation correlates with a loss of HIF-1α expression which itself occurs in the face of increased tissue hypoxia.

Hai Tao Yuan - One of the best experts on this subject based on the ideXlab platform.

  • Dysmorphogenesis of kidney cortical Peritubular Capillaries in angiopoietin-2-deficient mice.
    American Journal of Pathology, 2004
    Co-Authors: Jolanta E. Pitera, Adrian S. Woolf, Nicholas W. Gale, George D. Yancopoulos, Hai Tao Yuan
    Abstract:

    Angiopoietin-2 (Ang-2) modulates Tie-2 receptor activation. In mouse kidney maturation, Ang-2 is expressed in arteries, with lower levels in tubules, whereas Tie-2 is expressed by endothelia. We hypothesized that Ang-2 deficiency disrupts kidney vessel patterning. The normal renal cortical Peritubular space contains fenestrated Capillaries, which have few pericytes; they receive water and solutes which proximal tubules reclaim from the glomerular filtrate. In wild-type neonates, α smooth muscle actin (αSMA), platelet-derived growth factor receptor β (PDGFRβ), and desmin-expressing cells were not prominent in this compartment. In Ang-2 null mutants, αSMA, desmin, and PDGFRβ prominently immunolocalized in cortical Peritubular locations. Some αSMA-positive cells were closely associated with CD31- and Tie-2-positive Peritubular capillary endothelia, and some of the αSMA-positive cells expressed PDGFRβ, desmin, and neural/glial cell 2 (NG2), consistent with a pericyte-like identity. Immunoblotting suggested an increase of total and tyrosine-phosphorylated Tie-2 proteins in null mutant versus wild-type kidneys, and electron microscopy confirmed disorganized Capillaries and adjacent cells in cortical Peritubular spaces in mutant neonate kidneys. Hence, Ang-2 deficiency causes dysmorphogenesis of cortical Peritubular Capillaries, with adjacent cells expressing pericyte-like markers; we speculate the latter effect is caused by disturbed paracrine signaling between endothelial and surrounding mesenchymal precursor cells.

  • Peritubular capillary loss after mouse acute nephrotoxicity correlates with down regulation of vascular endothelial growth factor a and hypoxia inducible factor 1α
    American Journal of Pathology, 2003
    Co-Authors: Hai Tao Yuan, Jolanta E. Pitera, Xiaozhong Li, David A Long, Adrian S. Woolf
    Abstract:

    Although the response of kidneys acutely damaged by ischemia or toxins is dominated by epithelial destruction and regeneration, other studies have begun to define abnormalities in the cell biology of the renal microcirculation, especially with regard to Peritubular Capillaries. We explored the integrity of Peritubular Capillaries in relation to expression of vascular endothelial growth factor (VEGF)-A, hypoxia-inducible factor (HIF)-α proteins, and von Hippel-Lindau protein (pVHL) in mouse folic acid nephropathy, a model in which acute tubular damage is followed by partial regeneration and progression to patchy chronic histological damage. Throughout a period of 14 days, in areas of cortical tubular atrophy and interstitial fibrosis, loss of VEGFR-2 and platelet endothelial cell adhesion molecule-expressing Peritubular Capillaries was preceded by marked decreases in VEGF-A transcript and protein levels. Nephrotoxicity was associated with tissue hypoxia, especially in regenerating tubules, as assessed by an established in situ method. Despite the hypoxia, levels of HIF-1α, a protein known to up-regulate VEGF-A, were reduced. During the course of nephrotoxicity, levels of pVHL, a factor that destabilizes HIF-1α, increased significantly. We speculate that that down-regulation of VEGF-A may be functionally-implicated in the progressive attrition of Peritubular Capillaries in areas of tubular atrophy and interstitial fibrosis; VEGF-A down-regulation correlates with a loss of HIF-1α expression which itself occurs in the face of increased tissue hypoxia.

Poul Faarup - One of the best experts on this subject based on the ideXlab platform.

  • structural evidence for counter current flow in proximal tubules versus pertitubular Capillaries in the rat kidney evaluation of the counter current mechanism between the proximal convoluted tubules and the Peritubular Capillaries in the rat nephron
    Apmis, 2000
    Co-Authors: Poul Faarup, Nielshenrik Holsteinrathlou, Viktor Hegedus
    Abstract:

    BACKGROUND: In spite of the very high exchange of water and solutes between the proximal tubules and the Peritubular Capillaries, very little is known about flow directions in these two interrelated structures. We therefore developed a morphological technique suitable for the quantitative evaluation of a counter-current system between the proximal convoluted tubules and the Peritubular Capillaries in rat renal cortex. METHODS: In male pentothal-anesthetized Wistar rats (body weight 200-250 g), India ink was injected into the aorta above the renal arteries, followed by instant freezing of the right kidney in isopentane at -165 degrees C, and subsequent freeze-substitution in alcohol. In microscopic slides from kidneys in which only 20-55% of the cortical Peritubular capillary loops was filled with ink--representing the arterial end of the Capillaries--and in which the proximal tubular segmentation could be identified in PAS-stained sections, the segments of the convoluted proximal tubules were quantitatively compared with regard to the presence of ink-stained and unstained Peritubular Capillaries in nephrons from the whole renal cortex. RESULTS: In the microscopic specimens of the five animals used both the loops from the first segment (P1) of the proximal convoluted tubule and those of the second segment (P2) were systematically packed closely together, the transitional segment (P1-2) being interposed between the groups. Around the loops of P1, 8%+/-2% of the Capillaries was stained with India ink. In contrast, surrounding the P2 loops 67%+/-5% of the Capillaries contained ink, significantly exceeding that for P1 (p<0.01). CONCLUSION: Throughout the rat renal cortex, the most proximal fraction of the Peritubular Capillaries surrounds the second segments of the proximal convoluted tubules, while the first tubular segments are surrounded by the more distal fraction of the Peritubular Capillaries. Consequently, the flows in the Peritubular Capillaries and in the proximal convoluted tubules in the rat renal cortex are systematically arranged as a counter-current system. This feature was previously identified only in superficial nephrons.

  • Structural evidence for counter-current flow in proximal tubules versus pertitubular Capillaries in the rat kidney. Evaluation of the counter-current mechanism between the proximal convoluted tubules and the Peritubular Capillaries in the rat nephron
    Apmis, 2000
    Co-Authors: Poul Faarup, Niels-henrik Holstein-rathlou, Viktor Hegedus
    Abstract:

    BACKGROUND: In spite of the very high exchange of water and solutes between the proximal tubules and the Peritubular Capillaries, very little is known about flow directions in these two interrelated structures. We therefore developed a morphological technique suitable for the quantitative evaluation of a counter-current system between the proximal convoluted tubules and the Peritubular Capillaries in rat renal cortex. METHODS: In male pentothal-anesthetized Wistar rats (body weight 200-250 g), India ink was injected into the aorta above the renal arteries, followed by instant freezing of the right kidney in isopentane at -165 degrees C, and subsequent freeze-substitution in alcohol. In microscopic slides from kidneys in which only 20-55% of the cortical Peritubular capillary loops was filled with ink--representing the arterial end of the Capillaries--and in which the proximal tubular segmentation could be identified in PAS-stained sections, the segments of the convoluted proximal tubules were quantitatively compared with regard to the presence of ink-stained and unstained Peritubular Capillaries in nephrons from the whole renal cortex. RESULTS: In the microscopic specimens of the five animals used both the loops from the first segment (P1) of the proximal convoluted tubule and those of the second segment (P2) were systematically packed closely together, the transitional segment (P1-2) being interposed between the groups. Around the loops of P1, 8%+/-2% of the Capillaries was stained with India ink. In contrast, surrounding the P2 loops 67%+/-5% of the Capillaries contained ink, significantly exceeding that for P1 (p